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52-820: Khardung La ( Tibetan : མཁར་གདོང་ལ་ , Wylie : mkhar gdong la , THL : khar dong la ) or Khardung Pass is a mountain pass in the Leh district of the Indian union territory of Ladakh . The pass is on the Ladakh Range , north of Leh , and connects the Indus river valley and the Shyok river valley. It also forms the gateway to the Nubra Valley , beyond which lies the Siachen Glacier . A motorable road through

104-580: A daily bus service to Nubra Valley passes over Khardung La which may also be reached by a hired car with an experienced driver or by motorcycle . The two bases on either side of Khardung La are North Pullu and South Pullu. An Inner Line Permit (ILP), which can be acquired at the District Commissioner's office in Leh, is required for tourists (not needed for Ladakh citizens). People are required to check in en route and must provide photocopies of

156-473: A proton than to donate one, but it is also far less likely for it to do either, thus bicarbonate will be the major species at physiological pH. Under normal conditions in the proximal convoluted tubule of the kidney, most of the carbonic acid (H 2 CO 3 ) produced intracellularly by the action of carbonic anhydrase quickly dissociates in the cell to bicarbonate (HCO 3 ) and an H ion (a proton ), as previously mentioned. The bicarbonate (HCO 3 ) exits at

208-421: A result of this whole process, there is a greater net balance of H in the urinary lumen than bicarbonate (HCO 3 ), and so this space is more acidic than physiologic pH. Thus, there is an increased likelihood that any bicarbonate (HCO 3 ) that was left over in the lumen diffuses back into the cell as carbonic acid, CO 2 , or H 2 O. In short, under normal conditions, the net effect of carbonic anhydrase in

260-458: A space. Spaces are not used to divide words. The Tibetan alphabet has thirty basic letters, sometimes known as "radicals", for consonants. As in other Indic scripts , each consonant letter assumes an inherent vowel ; in the Tibetan script it is /a/. The letter ཨ is also the base for dependent vowel marks. Although some Tibetan dialects are tonal , the language had no tone at the time of

312-496: A written tradition. Amdo Tibetan was one of a few examples where Buddhist practitioners initiated a spelling reform. A spelling reform of the Ladakhi language was controversial in part because it was first initiated by Christian missionaries. In the Tibetan script, the syllables are written from left to right. Syllables are separated by a tsek (་); since many Tibetan words are monosyllabic, this mark often functions almost as

364-458: Is a clear indication, as it could lower intracranial pressure further. A 2012 review and meta-analysis found that there was "limited supporting evidence" but that acetazolamide "may be considered" for the treatment of central (as opposed to obstructive) sleep apnea . It has also been used to prevent methotrexate -induced kidney damage by alkalinizing the urine, hence speeding up methotrexate excretion by increasing its solubility in urine. There

416-410: Is above most other consonants, thus རྐ rka. However, an exception to this is the cluster རྙ /ɲa/. Similarly, the consonants ར /ra/, and ཡ /ja/ change form when they are beneath other consonants, thus ཀྲ /ʈ ~ ʈʂa/; ཀྱ /ca/. Besides being written as subscripts and superscripts, some consonants can also be placed in prescript, postscript, or post-postscript positions. For instance,

468-622: Is called umê script . This writing system is used across the Himalayas and Tibet . The script is closely linked to a broad ethnic Tibetan identity, spanning across areas in India , Nepal , Bhutan and Tibet. The Tibetan script is of Brahmic origin from the Gupta script and is ancestral to scripts such as Lepcha , Marchen and the multilingual ʼPhags-pa script , and is also closely related to Meitei . According to Tibetan historiography,

520-666: Is designed as a simple means for inputting Dzongkha text on computers. This keyboard layout was standardized by the Dzongkha Development Commission (DDC) and the Department of Information Technology (DIT) of the Royal Government of Bhutan in 2000. It was updated in 2009 to accommodate additional characters added to the Unicode & ISO 10646 standards since the initial version. Since

572-465: Is how the clinical diuretic effect is achieved, which reduces blood volume and thus preload on the heart to improve contractility and reduce blood pressure, or achieve other desired clinical effects of reduced blood volume such as reducing edema or intracranial pressure. An early description of this compound (as 2-acetylamino-1,3,4-thiadiazole-5-sulfonamide) and its synthesis has been patented. Smaller clinical trials have also shown promising results in

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624-626: Is in the diuretic and carbonic anhydrase inhibitor families of medication. It works by decreasing the formation of hydrogen ions and bicarbonate from carbon dioxide and water. Acetazolamide came into medical use in 1952. It is on the World Health Organization's List of Essential Medicines . Acetazolamide is available as a generic medication . It is used in the treatment of glaucoma , drug-induced edema , heart failure-induced edema, epilepsy and in reducing intraocular pressure after surgery. It has also been used in

676-431: Is possible that it might interact with: Acetazolamide is a carbonic anhydrase inhibitor , hence causing the accumulation of carbonic acid . Carbonic anhydrase is an enzyme found in red blood cells and many other tissues that catalyses the following reaction: hence lowering blood pH, by means of the following reaction that carbonic acid undergoes: which has a pK a of 6.3. The mechanism of diuresis involves

728-528: Is simply read as it usually is and has no effect on the pronunciation of the consonant to which it is subjoined, for example ཀ་ཝ་ཟུར་ཀྭ (IPA: /ka.wa.suː.ka/). The vowels used in the alphabet are ཨ /a/, ཨི /i/, ཨུ /u/, ཨེ /e/, and ཨོ /o/. While the vowel /a/ is included in each consonant, the other vowels are indicated by marks; thus ཀ /ka/, ཀི /ki/, ཀུ /ku/, ཀེ /ke/, ཀོ /ko/. The vowels ཨི /i/, ཨེ /e/, and ཨོ /o/ are placed above consonants as diacritics, while

780-560: Is solely for the consonants ད /tʰa/ and ས /sa/. The head ( མགོ in Tibetan, Wylie: mgo ) letter, or superscript, position above a radical is reserved for the consonants ར /ra/, ལ /la/, and ས /sa/. The subscript position under a radical can only be occupied by the consonants ཡ /ja/, ར /ra/, ལ /la/, and ཝ /wa/. In this position they are described as བཏགས (Wylie: btags , IPA: /taʔ/), in Tibetan meaning "hung on/affixed/appended", for example བ་ཡ་བཏགས་བྱ (IPA: /pʰa.ja.taʔ.t͡ʃʰa/), except for ཝ , which

832-403: Is some evidence to support its use to prevent hemiplegic migraine . Acetazolamide is also used for the treatment of acute mountain sickness. In the prevention or treatment of mountain sickness, acetazolamide inhibits the ability of the kidneys to reabsorb bicarbonate , the conjugate base of carbonic acid . Increasing the amount of bicarbonate excreted in the urine leads to acidification of

884-461: Is taken by mouth or injection into a vein . Acetazolamide is a first generation carbonic anhydrase inhibitor and it decreases the ocular fluid and osmolality in the eye to decrease intraocular pressure. Common side effects include numbness, ringing in the ears , loss of appetite, vomiting, and sleepiness. It is not recommended in those with significant kidney problems , liver problems , or who are allergic to sulfonamides . Acetazolamide

936-898: The Latin script . Multiple Romanization and transliteration systems have been created in recent years, but do not fully represent the true phonetic sound. While the Wylie transliteration system is widely used to Romanize Standard Tibetan , others include the Library of Congress system and the IPA-based transliteration (Jacques 2012). Below is a table with Tibetan letters and different Romanization and transliteration system for each letter, listed below systems are: Wylie transliteration (W), Tibetan pinyin (TP), Dzongkha phonetic (DP), ALA-LC Romanization (A) and THL Simplified Phonetic Transcription (THL). The first version of Microsoft Windows to support

988-518: The 9th-century spoken Tibetan, and current pronunciation. This divergence is the basis of an argument in favour of spelling reform , to write Tibetan as it is pronounced ; for example, writing Kagyu instead of Bka'-rgyud . The nomadic Amdo Tibetan and the western dialects of the Ladakhi language , as well as the Balti language , come very close to the Old Tibetan spellings. Despite that,

1040-697: The Indus, divides, one fork going south along the river's edge to Spitok, Khalatse and Khargil, the other turning north to Leh, the Khardong Pass (...), and Yarkand, an ancient trading center of Sinkiang." He continues, "Leh is on a historic caravan route that leads not only to Yarkand in Sinkiang but to Lhasa in Tibet. (...) the stream of trade. Wool, silver, felts, tea, candy, skins, velvets, silk, gold, carpets, musk, coral , borax , jade cups, salt came down from

1092-482: The King which were afterward translated. In the first half of the 7th century, the Tibetan script was used for the codification of these sacred Buddhist texts, for written civil laws, and for a Tibetan Constitution. A contemporary academic suggests that the script was instead developed in the second half of the 11th century. New research and writings also suggest that there were one or more Tibetan scripts in use prior to

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1144-522: The North Pullu checkpoint about 15 km beyond the pass the roadway was primarily loose rock, dirt, and occasional rivulets of snow melt. Now, all the way is properly paved. The road approaching the Nubra Valley is very well maintained (except in a few places where washouts or falling rock occur). Hired vehicles (two and four-wheel-drive), heavy trucks , and motorcycles regularly travel into

1196-439: The Nubra Valley, though special permits are required to be arranged for travellers. The 5,359 m (17,582 ft) elevation measure from hundreds of GPS surveys matches SRTM data, ASTER GDEM data, and Russian topographic mapping. It is broadly consistent with numerous GPS reports. The nearest sizable town is Leh . Leh is connected by road from Manali and Srinagar, and daily flights are operated from Delhi. From Leh,

1248-732: The Tibetan keyboard layout is MS Windows Vista . The layout has been available in Linux since September 2007. In Ubuntu 12.04, one can install Tibetan language support through Dash / Language Support / Install/Remove Languages, the input method can be turned on from Dash / Keyboard Layout, adding Tibetan keyboard layout. The layout applies the similar layout as in Microsoft Windows. Mac OS -X introduced Tibetan Unicode support with OS-X version 10.5 and later, now with three different keyboard layouts available: Tibetan-Wylie, Tibetan QWERTY and Tibetan-Otani. The Dzongkha keyboard layout scheme

1300-490: The Tibetan script was developed during the reign of King Songtsen Gampo by his minister Thonmi Sambhota , who was sent to India with 16 other students to study Buddhism along with Sanskrit and written languages. They developed the Tibetan script from the Gupta script while at the Pabonka Hermitage . This occurred c.  620 , towards the beginning of the king's reign. There were 21 Sutra texts held by

1352-439: The amount of oxygen in the blood. Acetazolamide is not an immediate cure for acute mountain sickness; rather, it speeds up (or, when taking before traveling, forces the body to early start) part of the acclimatization process which in turn helps to relieve symptoms. Acetazolamide is still effective if started early in the course of mountain sickness. As prevention, it is started one day before travel to altitude and continued for

1404-509: The arrangement of keys essentially follows the usual order of the Dzongkha and Tibetan alphabet, the layout can be quickly learned by anyone familiar with this alphabet. Subjoined (combining) consonants are entered using the Shift key. The Dzongkha (dz) keyboard layout is included in Microsoft Windows, Android, and most distributions of Linux as part of XFree86 . Tibetan was originally one of

1456-472: The basal portion of the cell via sodium (Na ) symport and chloride (Cl ) antiport and re-enters circulation, where it may accept a proton if blood pH decreases, thus acting as a weak, basic buffer. The remaining H left over from the intracellular production of carbonic acid (H 2 CO 3 ) exits the apical (urinary lumen) portion of the cell by Na antiport, acidifying the urine. There, it may join with another bicarbonate (HCO 3 ) that dissociated from its H in

1508-407: The basic Tibetan alphabet to represent different sounds. In addition to the use of supplementary graphemes, the rules for constructing consonant clusters are amended, allowing any character to occupy the superscript or subscript position, negating the need for the prescript and postscript positions. Romanization and transliteration of the Tibetan script is the representation of the Tibetan script in

1560-408: The blood becomes acidic, causing compensatory hyperventilation with deep respiration (Kussmaul breathing), increasing levels of oxygen and decreasing levels of carbon dioxide in the blood. In the eye this results in a reduction in aqueous humour . Bicarbonate (HCO 3 ) has a pK a of 10.3 with carbonate (CO 3 ), far further from physiologic pH (7.35–7.45), and so it is more likely to accept

1612-447: The blood. Because the body senses CO 2 concentration indirectly via blood pH (increase in CO 2 causes a decrease in pH), acidifying the blood through decreased renal reabsorption of bicarbonate is sensed as an increase in CO 2 . This, in turn, causes the body to increase minute ventilation (the amount of air breathed per minute) in order to "breathe off" CO 2 , which in turn increases

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1664-418: The consonants ག /kʰa/, ད /tʰa/, བ /pʰa/, མ /ma/ and འ /a/ can be used in the prescript position to the left of other radicals, while the position after a radical (the postscript position), can be held by the ten consonants ག /kʰa/, ན /na/, བ /pʰa/, ད /tʰa/, མ /ma/, འ /a/, ར /ra/, ང /ŋa/, ས /sa/, and ལ /la/. The third position, the post-postscript position

1716-626: The effects of nursing mothers taking acetazolamide. Therapeutic doses create low levels in breast milk and are not expected to cause problems in infants. Common adverse effects of acetazolamide include the following: paraesthesia , fatigue, drowsiness, depression, decreased libido, bitter or metallic taste, nausea, vomiting, abdominal cramps, diarrhea, black stool, polyuria , kidney stones , metabolic acidosis and electrolyte changes ( hypokalemia , hyponatremia ). Whereas less common adverse effects include Stevens–Johnson syndrome , anaphylaxis and blood dyscrasias . Contraindications include: It

1768-480: The first two days at altitude. Acetazolamide is pregnancy category B3 in Australia, which means that studies in rats, mice and rabbits in which acetazolamide was given intravenously or orally caused an increased risk of fetal malformations, including defects of the limbs. Despite this, there is insufficient evidence from studies in humans to either support or discount this evidence. Limited data are available on

1820-592: The grammar of these dialectical varieties has considerably changed. To write the modern varieties according to the orthography and grammar of Classical Tibetan would be similar to writing Italian according to Latin orthography, or to writing Hindi according to Sanskrit orthogrophy. However, modern Buddhist practitioners in the Indian subcontinent state that the classical orthography should not be altered even when used for lay purposes. This became an obstacle for many modern Tibetic languages wishing to modernize or to introduce

1872-418: The internet report that acetazolamide can be used to treat dural ectasia in individuals with Marfan syndrome , the only supporting evidence for this assertion exists from a small study of 14 patients which was not peer-reviewed or submitted for publication. Several published cases of intracranial hypotension related to Marfan syndrome would warrant caution in using acetazolamide in these patients unless there

1924-452: The introduction of the script by Songtsen Gampo and Thonmi Sambhota . The incomplete Dunhuang manuscripts are their key evidence for their hypothesis, while the few discovered and recorded Old Tibetan Annals manuscripts date from 650 and therefore post-date the c. 620 date of development of the original Tibetan script. Three orthographic standardisations were developed. The most important, an official orthography aimed to facilitate

1976-409: The lumen of the urinary space only after exiting the proximal convoluted kidney cells/glomerulus as carbonic acid (H 2 CO 3 ) because bicarbonate (HCO 3 ) itself can not diffuse across the cell membrane in its polar state. This will replenish carbonic acid (H 2 CO 3 ) so that it then may be reabsorbed into the cell as itself or CO 2 and H 2 O (produced via a luminal carbonic anhydrase). As

2028-483: The north. Cotton goods, shawls, brocades, opium, indigo, plumes, shoes, pearls, ginger, cloves, pepper, honey, tobacco, sugar cane, barley rice, wheat, corn came up from the south." During World War II there was an attempt to transfer war material to China through this route. Khardung La is 39 km by road from Leh. Earlier, the first 24 km, as far as the South Pullu check point, were paved. From there to

2080-411: The official Leh site. Khardung La has an arctic tundra climate ( ET ) with short, cool summers and long, very cold winters. Tibetan script The Tibetan script has also been used for some non-Tibetic languages in close cultural contact with Tibet, such as Thakali , Nepali and Old Turkic . The printed form is called uchen script while the hand-written cursive form used in everyday writing

2132-588: The pass was built in 1976, and opened to public motor vehicles in 1988. Maintained by the Border Roads Organisation , the pass is strategically important to India as it is used to carry supplies to the Siachen Glacier. The road is one of the world's highest motoroable roads. The elevation of Khardung La is 5,359 m (17,582 ft). Local summit signs and dozens of stores selling shirts in Leh incorrectly claim its elevation to be in

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2184-566: The permits to be deposited at each checkpoint. Altitude sickness is a serious health concern for people not acclimatised to high altitudes. From 2022 minimum two days mandatory acclimatisation in Leh is required before crossing the pass Preventive medication, i.e. acetazolamide , can be used in this period to boost acclimatisation. The road is often subject to long delays due to traffic congestion on narrow one-lane sections, washouts, avalanches and road accidents, but with no permanent winter closure. Updates on road conditions can be found at

2236-418: The proximal tubule of the kidney. The enzyme carbonic anhydrase is found here, allowing the reabsorption of bicarbonate, sodium, and chloride. By inhibiting this enzyme, these ions are excreted, along with excess water, lowering blood pressure, intracranial pressure, and intraocular pressure. A general side effect of carbonic anhydrase inhibitors is loss of potassium due to this function. By excreting bicarbonate,

2288-404: The radical ཀ /ka/ and see what happens when it becomes ཀྲ /kra/ or རྐ /rka/ (pronounced /ka/). In both cases, the symbol for ཀ /ka/ is used, but when the ར /ra/ is in the middle of the consonant and vowel, it is added as a subscript. On the other hand, when the ར /ra/ comes before the consonant and vowel, it is added as a superscript. ར /ra/ actually changes form when it

2340-453: The script's invention, and there are no dedicated symbols for tone. However, since tones developed from segmental features, they can usually be correctly predicted by the archaic spelling of Tibetan words. One aspect of the Tibetan script is that the consonants can be written either as radicals or they can be written in other forms, such as subscript and superscript forming consonant clusters . To understand how this works, one can look at

2392-768: The scripts in the first version of the Unicode Standard in 1991, in the Unicode block U+1000–U+104F. However, in 1993, in version 1.1, it was removed (the code points it took up would later be used for the Burmese script in version 3.0). The Tibetan script was re-added in July, 1996 with the release of version 2.0. The Unicode block for Tibetan is U+0F00–U+0FFF. It includes letters, digits and various punctuation marks and special symbols used in religious texts: Acetazolamide Acetazolamide , sold under

2444-420: The trade name Diamox among others, is a medication used to treat glaucoma , epilepsy , acute mountain sickness , periodic paralysis , idiopathic intracranial hypertension (raised brain pressure of unclear cause), heart failure and to alkalinize urine. It may be used long term for the treatment of open angle glaucoma and short term for acute angle closure glaucoma until surgery can be carried out. It

2496-467: The translation of Buddhist scriptures emerged during the early 9th century. Standard orthography has not been altered since then, while the spoken language has changed by, for example, losing complex consonant clusters . As a result, in all modern Tibetan dialects and in particular in the Standard Tibetan of Lhasa , there is a great divergence between current spelling, which still reflects

2548-466: The treatment of altitude sickness , Ménière's disease , increased intracranial pressure and neuromuscular disorders. Acetazolamide is also used in the critical care setting to stimulate respiratory drive in patients with chronic obstructive pulmonary disease as an off-label indication. In epilepsy, the main use of acetazolamide is in menstrual-related epilepsy and as an add on to other treatments in refractory epilepsy. Though various websites on

2600-577: The urinary lumen and cells of the proximal convoluted tubule is to acidify the urine and transport bicarbonate (HCO 3 ) into the body. Another effect is excretion of Cl as it is needed to maintain electroneutrality in the lumen, as well as the reabsorption of Na into the body. Thus, by disrupting this process with acetazolamide, urinary Na and bicarbonate (HCO 3 ) are increased, and urinary H and Cl are decreased. Inversely, serum Na and bicarbonate (HCO 3 ) are decreased, and serum H and Cl are increased. H 2 O generally follows sodium, and so this

2652-530: The vicinity of 5,602 m (18,379 ft) and that it is the world's second highest motorable pass. Khardong La is historically important as it lies on the major caravan route from Leh to Kashgar in Central Asia . About 10,000 horses and camels used to take the route annually, and a small population of Bactrian camels can still be seen at Hunder, in the area north of the pass. In the early 1950s, William O. Douglas described "the trail, after crossing

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2704-512: The vowel ཨུ /u/ is placed underneath consonants. Old Tibetan included a reversed form of the mark for /i/, the gigu 'verso', of uncertain meaning. There is no distinction between long and short vowels in written Tibetan, except in loanwords , especially transcribed from the Sanskrit . The Tibetan alphabet, when used to write other languages such as Balti , Chinese and Sanskrit , often has additional and/or modified graphemes taken from

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